title: High binding affinity of electronegative LDL to human aortic proteoglycans depends on its aggregation level.
abstract: Electronegative LDL [LDL(-)] is an atherogenic subfraction of plasma LDL that has increased apolipoprotein E (apoE) and apoC-III content, high density, and increased susceptibility to aggregation. These characteristics suggest that LDL(-) could bind to proteoglycans (PGs); therefore, our aim was to evaluate its affinity to PGs. Binding of LDL(-) and native LDL [LDL(+)] to human aortic PGs was determined by precipitation of LDL-glycosaminoglycan complexes, LDL incubation in PG-coated microtiter wells, and affinity chromatography on PG column. All methods showed that LDL(-) had higher binding affinity to PGs than did LDL(+). PG capacity to bind LDL(-) was increased approximately 4-fold compared with LDL(+) in precipitation and microtiter assays. Chromatography on PG column showed LDL(-) to consist of two subpopulations, one with higher and one with lower PG binding affinity than LDL(+). Unexpectedly, the lower PG affinity subpopulation had increased apoE and apoC-III content. In contrast, the high PG affinity subpopulation presented phospholipase C (PLC)-like activity and increased aggregation. These results suggest that PLC-like activity could alter LDL lipid composition, thereby promoting particle aggregation and binding to PGs. This propensity of a subpopulation of LDL(-) to bind to PGs could facilitate its retention in the extracellular matrix of arterial intima and contribute to atherosclerosis progression.
authors.affiliation: Servei de Bioquímica, Institut de Recerca, Hospital de la Santa Creu i Sant Pau, C/ Antoni Maria Claret 167, 08025 Barcelona, Spain; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bancells
authors.affiliation: Servei de Bioquímica, Institut de Recerca, Hospital de la Santa Creu i Sant Pau, C/ Antoni Maria Claret 167, 08025 Barcelona, Spain.
authors.forename: Sònia
authors.initials: S
authors.lastname: Benítez
authors.affiliation: National Public Health Institute and FIMM, Institute for Molecular Medicine Finland, Biomedicum, Haartmaninkatu 8, 00290 Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.affiliation: Servei de Bioquímica, Institut de Recerca, Hospital de la Santa Creu i Sant Pau, C/ Antoni Maria Claret 167, 08025 Barcelona, Spain; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Ordóñez-Llanos
authors.affiliation: Wihuri Research Institute, Kalliolinnantie 4, 00140 Helsinki, Finland.
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Villegas
authors.affiliation: Servei de Bioquímica, Institut de Recerca, Hospital de la Santa Creu i Sant Pau, C/ Antoni Maria Claret 167, 08025 Barcelona, Spain. Electronic address: jsanchezq@santpau.cat.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Sánchez-Quesada
authors.affiliation: Wihuri Research Institute, Kalliolinnantie 4, 00140 Helsinki, Finland.
authors.forename: Katariina
authors.initials: K
authors.lastname: O O Rni
mesh_terms: D001011:Aorta / Q000378:metabolism*; D053305:Apolipoprotein C-III / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D002846:Chromatography, Affinity; D004563:Electrochemistry; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D053305:Apolipoprotein C-III; D001057:Apolipoproteins E; D006025:Glycosaminoglycans; D008077:Lipoproteins, LDL; D046912:Multiprotein Complexes; D011509:Proteoglycans; D010738:Type C Phospholipases; D013108:Sphingomyelin Phosphodiesterase